The present proposal is directed to the mechanisms which control calcium efflux from the sarcoplasmic reticulum (SR) of heart and skeletal muscle. This research will examine the relationship between Ca efflux and the amount and characteristics of the phosphorylated Ca pump ATPase protein in isolated SR vesicles to test the hypothesis that a portion of the Ca pump ATPase reaction is utilized by these membranes also to regulate the "downhill" movement of Ca from the interior of the vesicles. The role of the energy donor (ATP, acetyl phosphate) and phosphate in these reactions will also be examined. The relationship between proteins of the SR other than the ATPase protein in governing Ca efflux will be examined in studies where different fractions of muscle microsomes are separated by density-gradient ultracentrifugation. These studies will relate Ca influx-efflux characteristics to the presence or absence of proteins such as "Calsequestrin" and the "Ca-Binding Protein". Chemical cross-linking studies will be used to evaluate the possibility that changing Ca influx-efflux behavior is related to monomerization-oligomerization of the SR proteins. These studies may add to our understanding of the mechanisms involved in excitation-contraction coupling and the control of myocardial contractility. These data may also be of relevance to the control of ionic fluxes in other membranes.